Background: HSP90B1, a member of the heat-shock protein 90 family, plays a vital role as a molecular chaperone for oncogenes and stimulates tumour growth. However, its role in various cancers remains unexplored. Methods: Using the cancer genome atlas, gene expression omnibus the Human Protein Atlas databases and various other bioinformatic tools, this study investigated the involvement of HSP90B1 in 33 different tumour types. Results: The over-expression of HSP90B1 generally predicted poor overall survival and disease-free survival for patients with tumours, such as adrenocortical carcinoma, bladder urothelial carcinoma, kidney renal papillary cell carcinoma, and lung adenocarcinoma. In this study, HSP90B1 was highly expressed in the majority of tumours. A comparison was made between the phosphorylation of HSP90B1 in normal and primary tumour tissues, and putative functional mechanisms in HSP90B1-mediated oncogenesis were investigated. Additionally, the mutation burden of HSP90B1 in cancer was evaluated along with the survival rate of patients with cancer patients. Conclusion: This first pan-cancer investigation reveals the oncogenic functions of HSP90B1 in various cancers.
Patients with advanced bladder cancer gradually become less sensitive to chemotherapeutic agents, leading to tumor recurrence. Initiating the senescence program in solid tumors may be an important means of improving short-term drug sensitivity. The important role of c-Myc in bladder cancer cell senescence was determined using bioinformatics methods. The response to cisplatin chemotherapy in bladder cancer sample was analyzed according to the Genomics of Drug Sensitivity in Cancer database. Cell Counting Kit-8 assay, clone formation assay, and senescence-associated β-galactosidase staining were used to assess bladder cancer cell growth, senescence, and sensitivity to cisplatin, respectively. Western blot and immunoprecipitation were performed to understand the regulation of p21 by c-Myc/HSP90B1. Bioinformatic analysis showed that c-Myc, a cellular senescence gene, was significantly associated with bladder cancer prognosis and sensitivity to cisplatin chemotherapy. c-Myc and HSP90B1 expression were highly correlated in bladder cancer. Reducing the level of c-Myc significantly inhibited bladder cancer cell proliferation, promoted cellular senescence, and enhanced cisplatin chemosensitivity. Immunoprecipitation assays confirmed that HSP90B1 interacted with c-Myc. Western blot analysis showed that reducing the level of HSP90B1 could redeem the p21 overexpression caused by c-Myc overexpression. Further studies showed that reducing HSP90B1 expression could alleviate the rapid growth and accelerate cellular senescence of bladder cancer cells caused by c-Myc overexpression, and that reducing HSP90B1 levels could also improve cisplatin sensitivity in bladder cancer cells. HSP90B1/c-Myc interaction regulates the p21 signaling pathway, which affects cisplatin chemosensitivity by modulating bladder cancer cell senescence.
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